Canthaxanthin (β,β-carotene-4,4′-dione) and astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) are red carotenoid pigments from the group of the xanthophylls which are described by the formula below (in each case the all-trans isomer is shown).

Astaxanthin, hereinafter also AXT, in contrast to canthaxanthin, has a center of asymmetry in the 3- and 3′-position and can therefore be present as a diastereomeric mixture of the (3R,3′R)-, (3S,3′S)- and (3S,3′R)-isomers, as a racemate of the (3R,3′R)- and the (3S,3′S)-isomer or in the form of the pure isomers. Synthetic AXT is frequently a mixture of the diastereomers (3S,3′S), (3R,3′S) and (3R,3′R). AXT obtained from natural sources can, depending on the respective natural source, be present in virtually pure (3S,3′S) or (3R,3′R) form. Likewise, enantiomerically pure astaxanthin is accessible by total synthesis.
Astaxanthin and canthaxanthin are primarily used as feed component for various animals, in particular for salmon and trout. Thus AXT has a vitamin-like activity acting as a result beneficially on the fertility and immune defense of the fish in breeding farms. Astaxanthin and canthaxanthin are permitted as feed additives to the fish food during the production of edible fish. Canthaxanthin and astaxanthin, however, are also used as food dyes, as nutriceuticals or cosmetics additives having antioxidant properties. AXT can protect the skin against the stress caused by UV radiation and acts in this function considerably more strongly than vitamin E. AXT supplements the protective action of sunscreen agents and cannot be washed off. Studies on animals permit the hypothesis that AXT lowers the blood sugar level and improves various parameters of the metabolic syndrome. In addition, in blood hypertension models, it leads to an increase in blood flow and of vascular tone. In addition, AXT appears to promote the formation of Connexin 43 and therefore has a chemoprotective action with respect to cancers (see A. L. Vine et al., Nutr. Cancer 52(1) (2005), 105-113).
Astaxanthin can be obtained on an industrial scale from blood-rain alga (Haematococcus pluvialis) or obtained from the shells of crustacia. Astaxanthin is generally obtained by extraction by means of dichloromethane (see, e.g. CN 102106448).
The production of synthetic astaxanthin, which is generally a mixture of the meso-(3R,3′S) form with the (3R,3′R)- and (3S,3′S) isomers is extensively described in the literature, e.g. in the monograph G. Britton, S. Liaanen-Jensen, H. Pfander (editors), Carotenoids, Vol. 2, Birkhauser Verlag, Basle, 1996, in particular p. 11, pp. 267 ff. and pp. 281 ff. and literature cited there, in various textbooks, such as B. Schäfer, Naturstoffe der chemischen Industrie [Natural materials of the chemical industry], Akademischer Verlag, Heidelberg, 2007, 427 ff. and literature cited there, and also in the patent literature, e.g. EP 1197483 or EP 1285912. Processes for producing canthaxanthin are described in the monograph G. Britton, S. Liaanen-Jensen, H. Pfander (editors), Carotenoids, Vol. 2, Birkhäuser Verlag, Basle, 1996, in particular p. 11, pp. 267 ff. and pp. 281 ff. and literature cited there, and also in Seyoung Choi et al., J. Org. Chem., 2005, 70 (8), p. 3328-333.
Astaxanthin and canthaxanthin have only low solubility in most organic solvents. The octanol-water partition coefficients log P (octanol/water) are in the same range: The log P of astaxanthin is 13,27 (The EFSA Journal 2005, 291, p. 10), the log P of canthaxanthin is 9,79 (FooDB data base, entry FDB015890) in contrast, their solubility in halogenated hydrocarbons such as dichloromethane or chloroform is adequate for many purposes. Therefore, the synthetic production of astaxanthin proceeds, at least in the final step, in a halogenated hydrocarbon such as dichloromethane, dichloroethane, chlorobenzene, trichloromethane, tetrachloroethane, tetrachloroethene or trichloroethane. Generally, halogenated hydrocarbons such as dichloromethane, dichloroethane or trichloromethane are used in the extraction of astaxanthin from natural sources. Therefore, astaxanthin generally comprises significant amounts of halogenated hydrocarbon as contaminants, which cannot be removed with usual auxiliaries. Halogenated hydrocarbons, however, are of toxicological concern. For many applications, in particular in those for pharmaceutical purposes, or for use in foods, strict limiting values with respect to halogenated hydrocarbons must be maintained. For instance, for example the content of dichloromethane in astaxanthin or canthaxanthin for many applications must not exceed a value of 600 ppm. For other halogenated hydrocarbons, likewise strict limiting values apply. Despite their comparatively high volatility, halogenated hydrocarbon contaminants in astaxanthin and canthaxanthin may be removed only with difficulty.
Further contaminants which occur, in particular, in the case of synthetic astaxanthin are organophosphorus compounds, in particular triphenylphosphine oxide, since many production methods comprise a Wittig reaction or a Horner-Emmons reaction. Thus, in industrial synthesis, astaxanthin is predominantly produced by reacting [5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexyl)-3-methyl-2,4-pentadienyl]triphenylphosphonium bromide or a corresponding Horner-Emmons derivative with 2,7-dimethyloctatrienedial, C10-dialdehyde, wherein triphenylphosphine oxide or, in the case of the Horner-Wadsworth-Emmons variant, the corresponding phosphonate is formed. The production of astaxanthin by reacting a 3-[5-(arylsulfonyl)-4-methylpenta-1,3-dienyl]-6-hydroxy-2,4,4-trimethyl-cyclohex-2-en-1-one with C10-dialdehyde in the context of a Julia-olefination, is likewise known in the literature (see G. Britton et al. loc. cit., p. 12 and pp. 103 ff.). Further contaminants might be canthaxanthin isomers, echinenone and other colored carotenoid impurities. Canthaxanthin isomers are e.g. 9Z-Canthaxanthin and 13Z-Canthaxanthin. Other colored carotenoid impurities are e.g. β-Carotene and β-Carotene derived degradation products with λmax in the range from 400 to 700 nm.
Comparable production processes are known for canthaxanthin, e.g. the reaction of [5-(2,6,6-trimethyl-3-oxo-1-cyclohexyl)-3-methyl-2,4-pentadienyl]triphenylphosphonium bromide or a corresponding Horner-Emmons derivative with C10-dialdehyde and also the reaction of 3-[5-(arylsulfonyl)-4-methylpenta-1,3-dienyl]-2,4,4-trimethylcyclohex-2-en-1-one with C10-dialdehyde in the context of a Julia-olefination. The production of canthaxanthin by reacting β-carotene with oxidizing agents (see, e.g. DE 2534805 and literature cited there) is likewise known.